PB2037: RESULTS FROM PIMMS, A UK MYELOMA RESEARCH ALLIANCE (UKMRA) STUDY OF OUTCOMES AND TOXICITY OF PANOBINOSTAT WITH BORTEZOMIB AND DEXAMETHASONE IN PATIENTS WITH RELAPSED MYELOMA IN A REAL WORLD SETTING
Authors: J. Waters, K. Boyd, S. Moore, J. Marawi, P. Bassett, C. Parrish, R. Benjamin
Journal: HemaSphere (2022)

Background: Following the PANORAMA-1 trial, Panobinostat was approved in 2016 for the treatment of relapsed/refractory multiple myeloma (RRMM) in combination with bortezomib and dexamethasone (Pan-Bor-Dex) following at least 2 prior regimens including bortezomib and an immunomodulatory imide drug (IMiD). Since then, there have been several new drug approvals for RRMM and the treatment landscape has therefore changed significantly with Pan-Bor-Dex being used at later stages of the disease. It is therefore important to evaluate the efficacy and toxicity of this regimen in a real world setting given that the patient population being treated may be quite different to that in the PANORAMA-1 trial. Furthermore dosing schedules and dose modifications vary considerably in practice and may play an important part in minimising toxicity, preventing drug discontinuation and potentially impacting on duration of response. Aims: The primary objective of this study was to determine the progression free survival (PFS) of RRMM patients in the UK receiving Pan-Bor-Dex. Secondary objectives were to assess overall response rate (ORR), depth of response, time to best response, duration of response, time to next treatment and overall survival as well as to assess incidence of grade ≥3 adverse events (AEs), dose modifications and impact on health care resource utilisation. Methods: This was a UKMRA retrospective, observational, multi-centre study conducted at hospitals across England and Wales. All patients who received at least 1 cycle of Pan-Bor-Dex at each site between 01 Jan 2016 and 01 Jan 2018 were enrolled in the study. 01 Jan 2020 was the data cut-off date and patients who had not progressed by this date were censored at this timepoint. Results: 219 patients were enrolled across 26 University and district general hospitals. The median age of the cohort was 69yrs (IQR 60-75) with 56% (n=106) aged ≥70yrs. The median number of prior treatment lines was 4 (IQR 3-5). 22% were refractory to a proteosomal inhibitor, 68% to an ImiD and and 5% to an anti-CD38 antibody. 54% had received an autologous stem cell transplant. Median number of cycles of Pan-Bor-Dex completed was 4 with 7.3% (n=16) of patients achieving the maximum 16 cycles approved by the National Institute of Health and Care Excellence (NICE). ORR was 61% (n=133) with 37% achieving a partial response, 19% (n=44) a very good partial response and 5% (n=7) a complete response. Median PFS was 4.2 months (95% CI, 3.5-6) (see Figure). Initial sub-group analyses showed a significant difference in PFS between age groups. Older patients ≥70yrs achieved a median PFS of 6 months compared to 3.5 months in patients <70yrs (p value 0.02). Toxicity led to discontinuation in 18% (n=38) of patients. Most frequent grade≥3 AEs included thrombocytopenia (59%), anaemia (39%), neutropenia (32%), diarrhoea (12%) and fatigue (12%). Image:Summary/Conclusion: In this UK real world study of RRMM patients from 2016-2018 we have shown that the Pan-Bor-Dex regimen despite being used, on average, as fifth line treatment resulted in an ORR of 61%, comparable to that seen in the PANORAMA-1 Trial where patients were less heavily pre-treated. The overall median PFS was 4.2 months, not dissimilar to other drug regimens in advanced stage myeloma. Further data will be presented at the meeting including results of multivariate analysis to identify baseline patient factors that correlate with PFS.